Opening Mechanism of G·T/U Pairs in DNA and RNA Duplexes: A Combined Study of Imino Proton Exchange and Molecular Dynamics Simulation

Abstract
The opening pathway of wobble pairs dG·T and rG·U has been investigated in four DNA and two RNA duplexes. Using NMR spectroscopy, we measured the imino proton exchange of both G(H1) and T/U(H3), catalyzed by ammonia, tris, and OH-, and we calculated the free energy surface related to G·T/U opening by molecular dynamics simulations. Taken together the experimental and theoretical results, we suggest that wobble pairs open through a coupled rotation of the bases toward the major groove where exchange of both imino protons takes place with the surrounding water.